Thrombosis [myocardial infarction (heart attack), cerebral infarction (stroke), and venous thromboembolism (blood clots in the arms and legs that may migrate to the lungs)] is thought to result from abnormalities in blood quality, blood flow, and vascular cells.
Abnormal levels of certain blood proteins are a risk factor for thrombosis. We have identified a potential mechanism for the association of elevated prothrombin with thrombosis: increased prothrombin produces clots with abnormally thin fibrin fibers. Since clots with thin fibers are resistant to fibrinolysis, we hypothesize that these clots are overly stable and prone to thrombosis. We further hypothesize that this mechanism is operant in thrombosis related to abnormal levels of other coagulation proteins. We want to compare the structure and stability of plasma clots from individuals and patients with different clotting protein levels.
We have found that cellular procoagulant activity modulates fibrin structure and stability. Since different cells express different levels of procoagulant, antithrombotic, and fibrinolytic activity, we hypothesize that clot quality reflects the cellular environment in which it is formed. We want to identify the unique cellular determinants of clot structure and characterize their effects on the clot’s mechanical and fibrinolytic stability. We also want to understand the role of cell-derived microparticles in blood clot formation, structure, and stability.
Abnormal blood flow is a risk factor for thrombosis. High flow increases platelet deposition on exposed subendothelium, whereas reduced flow is associated with an increased incidence of venous clots. We want to understand how blood flow modulates the formation, structure, and stability of clots.